The goal of this project is to understand the role of corticostriatal systems in the control of intake. We will use multi-electrode recording methods to study how neurons in medial and orbital parts of the rat frontal cortex and the ventral striatum encode the sensory properties and incentive values of food and the oral motor behaviors that enable food intake. By combining these recordings with pharmacological and optogenetic methods for reversible inactivation, we will examine the influences of the medial and orbital cortices on intake-related activity in the ventral striatum. Finally, we will collect some of the frst electro-physiological data from animals that are provided with chronic exposure to sugar-enriched diets. These studies will provide novel neuro- biological data on the control of intake that are crucial for understanding the worldwide obesity epidemic.
Aim 1 : Determine the specific contributions of the prelimbic and agranular insular cortices to the control of intake. We predict that perturbations of the prelimbic cortex (which projects to feeding-related areas of the midbrain) will reduce the duration of persistent bouts of licking in response to highly valued liquid foods. We further predict that perturbation of the agranular insular cortex (which projects robustly to the prelimbic cortex) will disrupt the ability of sensory cues to control intake, and wll lead to the loss of consummatory contrast effect. These predictions will be tested using fluorescent muscimol and an optogenetic neuronal silencer (ArchT) to reversibly inactivate the two cortical regions during a consummatory contrast task.
Aim 2 : Quantify the coding properties of intake-related neurons in the prelimbic and agranular insular cortices and the ventral striatum.
This Aim will use multi-site, multi-electrode recordings to examine (i) the time-course of changes in neuronal activity as animals learn to perform the consummatory contrast task, (ii) the encoding of nutrient identity and relative concentration and motor aspects of intake that are thought to reflect the palatability of food, and (iii) if chronic consumption of sugar and non-caloic sweeteners alters neuronal correlates of intake in these corticostriatal systems.
Aim 3 : Determine influences of the prelimbic and agranular insular cortices on the encoding of incentive value and the control of intake by neurons in the ventral striatum.
This Aim will examine how neuronal processing in the frontal cortex influences the encoding of taste and palatability information in the ventral striatum during the consummatory contrast task. We will combine methods for reversible inactivation and optogenetic perturbation in the cortex with multi-electrode recordings in the striatum.

Public Health Relevance

This project addresses several key issues for understanding the roles of taste and motivational processing in the neural control of food intake. We will examine 1) how disruptions of processing in the medial and orbital parts of the frontal cortex alter food intake, 2) how neurons in these cortical areas and the ventral striatum encode information related to taste and palatability of liquid foods and if these activities are changed b chronic consumption of carbohydrates and non-caloric sweeteners, and 3) how neurons in the ventral striatum are influenced by processing in the medial and orbital frontal cortices. The studies will be carried out using a rodent model, and the brain regions that will be studied are found in all mammals, including human beings. The project will provide mechanistic data on the neural processing of food reward and the control of oral intake. The results and broad conclusions will improve understanding of the central processing of taste information and brain basis of eating disorders and obesity.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
High Priority, Short Term Project Award (R56)
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Neurobiology of Motivated Behavior Study Section (NMB)
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Hyde, James F
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John B. Pierce Laboratory, Inc.
New Haven
United States
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